Articles about diseases

Archive for the ‘Surgery’ Category

“Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-Per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance)” was accepted as a rapid publication and published online this month by the Journal of Clinical Oncology. It will come out in print in September.

Because of its rapid growth rate, many women with triple-negative breast cancer receive chemotherapy to try to shrink it before undergoing surgery. With the standard treatment, the cancer is eliminated from the breast and lymph nodes in the armpit before surgery in about one third of women. This is referred to as a pathologic complete response (pCR). In patients who achieve pCR, the cancer is much less likely to come back, spread to other parts of the body, and cause the patient’s death than if the cancer survives the chemotherapy.

Sikov and his collaborators studied the addition of other drugs — carboplatin and/or bevacizumab — to the standard treatment regimen to see if they could increase response rates. More than 440 women from cancer centers across the country enrolled in this randomized clinical trial.

“Adding either of these medications significantly increased the percentage of women who achieved a pCR with the preoperative treatment. We hope that this means fewer women will relapse and die of their cancer, though the study is not large enough to prove this conclusively. Of the two agents we studied, we are more encouraged by the results from the addition of carboplatin, since it was associated with fewer and less concerning additional side effects than bevacizumab,” Sikov explains.

“More studies are planned to confirm the role of carboplatin in women with triple-negative breast cancer, and also to see if we can better identify which of these patients are most likely to benefit from its use. Until we have those results, medical oncologists who treat women with triple-negative breast cancer will have to decide whether the potential benefits of adding carboplatin outweigh its risks for each individual patient.”

Triple-negative breast cancer accounts for 15 to 20 percent of invasive breast cancers diagnosed in the United States each year, and is more common in younger women, African-Americans, Hispanics, and BRCA1-mutation carriers. With no identified characteristic molecular abnormalities that can be targeted with medication, the current standard of treatment is chemotherapy.

“Overall prognosis for women with this type of breast cancer remains inferior to that of other breast cancer subtypes, with higher risk of early relapse,” Sikov says.

The impact of soy consumption on breast cancer prevention and treatment is not clear although many women believe soy supplementation is beneficial based primarily on results from epidemiological studies. Moshe Shike, M.D., from the Department of Medicine at Memorial Sloan-Kettering Cancer Center and Weill Cornell Medical College in New York, NY, and colleagues conducted a randomized placebo-controlled study of the effects of soy supplementation on gene expression and markers of breast cancer risk among women diagnosed with invasive breast cancer. The study, run between 2003 and 2007 at Memorial Sloan-Kettering, enrolled a total of 140 patients who were randomized to either soy supplementation (soy protein) or placebo (milk protein), which lasted from the initial surgical consultation to the day before surgery (range=7-30 days). Tumor tissues from the diagnostic biopsy (pre-treatment) and at the time of resection (post-treatment) were then analyzed. They observed changes in several genes that promote cell cycle progression and cell proliferation among women in the soy group.

The authors conclude, “These data raise concern that soy may exert a stimulating effect on breast cancer in a subset of women.”

In an accompanying editorial, V. Craig Jordan, O.B.E., D.Sc., Ph.D., FMedSci, from the Department of Oncology at the Georgetown University Lombardi Comprehensive Cancer Center, Washington, DC, discusses how timing of soy supplementation is critical and reviews the evidence in the literature on phytoestrogens, which are contained in soy, and their known action in breast cancer. He writes, the study by Shike et al. “…illustrates the dangers of phytoestrogen consumption too soon, around menopause, but the biology of estrogen in estrogen-deprived conditions suggests that phytoestrogen could have benefit a decade after menopause.” He cautions that appropriate doses of soy and timing of consumption are critical considerations.

Researchers from The University of Manchester and The Christie NHS Foundation Trust — both part of Manchester Cancer Research Centre — say the test could be developed and used in hospitals within the next few years.

It would mean medics could see which patients could benefit from blood vessel-targeting drugs — such as bevacizumab — in addition to conventional therapy. Meanwhilehile others who are not going to benefit would be spared the time and side effects associated with having the drug.

The test would also help to reduce the cost to the NHS. Ovarian cancer has seen little increase in survival rates over the last few decades and scientists are seeking new treatment strategies to improve the standard approach of surgery and chemotherapy.

A recent advance has been to target the development of new blood vessels within the tumor — preventing the cancer from receiving the nutrients it needs to grow. Bevacizumab, one of the blood vessel-targeting drugs, has shown significant but modest improvements in patient survival so doctors are seeking ways to predict which patients are most likely to gain an advantage from this type of drug.

The research team looked at blood samples from patients enrolled in an international trial of bevacizumab. These patients received either standard chemotherapy treatment alone or chemotherapy plus the blood vessel-targeting drug.

Professor Gordon Jayson, Professor of Medical Oncology at The University of Manchester and Honorary Consultant at The Christie who jointly led the study, said: “We are keen to identify predictive biomarkers — measures that can indicate how well a patient will respond to treatment — so we can better target these drugs to patients most likely to benefit.”We investigated levels of a range of proteins in patients’ pre-treatment blood samples to see if any were associated with improved survival.”

The findings, published recently in the journal Clinical Cancer Research, show that two particular proteins — Ang1 and Tie2 — could be used in combination to predict patient response. Patients with high levels of Ang1 and low levels of Tie2 were most likely to benefit from bevacizumab.

Both these proteins are involved in controlling the formation of new blood vessels. Conversely, they found that patients with high levels of both proteins did not benefit from the additional drug.

Study co-author Professor Caroline Dive, from the Cancer Research UK Manchester Institute based at The University of Manchester, added: “We will now look to further explore the potential of using a blood test to personalise treatment for ovarian cancer patients.

Moving towards a more individualized treatment plan specific for each patient and their particular tumor is key to improving outcomes for patients while sparing those unlikely to benefit from potential side effects of therapy.”